Development of a vascular supply is a fundamental requirement for many physiological and pathological processes, particularly in actively growing tissues such as embryos and tumours. Such tissues satisfy a need for adequate blood supply by producing pro-angiogenic factors, which promote new blood vessel formation through a complex but orderly event known as angiogenesis. In the case of tumour growth, angiogenesis is believed to be crucial for the transition from hyperplasia to neoplasia and for providing nourishment for the growth and metastasis of the tumour. Thus, angiogenesis allows the tumour to grow beyond about 1 mm in diameter and also allows provides routes for the dissemination and subsequent recolonization of metastatic tumour cells.
Therefore, angiogenesis is emerging as an important biomarker and therapeutic target in cancer. While the majority of current non-invasive vascular imaging approaches can estimate vessel density, a recent comprehensive analysis of tumour vasculature in prostate cancers concluded that microvessel density is not linked to cancer-specific mortality after adjusting for clinical factors. The shape and size of vessels, however, is highly predictive and men with the most irregularly shaped vessels being 17.1 times more likely to develop lethal disease (Mucci et al., 2009, J Clin Oncol, 27:5627-33).
The process of vascular development is tightly regulated. To date, a significant number of molecules, mostly secreted factors produced by surrounding cells, have been shown to regulate endothelial cell differentiation, proliferation, migration and coalescence into cord-like structures. For example, vascular endothelial growth factor (VEGF) has been identified as a key factor involved in stimulating angiogenesis and in inducing vascular permeability. Anti-VEGF monoclonal antibodies or other inhibitors of VEGF action are promising candidates for the treatment of tumours and various intraocular neovascular disorders. Such antibodies are described, for example, in EP 817,648, WO 1998/45331, and WO 1998/45332.
In addition, an extracellular matrix (ECM)-associated protein designated epidermal growth factor-like 7 (EGFL7) has been shown to be expressed by endothelial cells and to have a role in angiogenesis (Parker et al., 2004, Nature, 428:754-758; Nichol and Stuhlmann, 2012, 119:1345-1352). While some have suggested the use of inhibitory anti-EGFL7 monoclonal antibodies for the treatment of tumours (U.S. 2007/0031437, U.S. 2009/0297512, U.S. 2010/0203041, and U.S. 2010/0285009), others have suggested the use of agonists of EGFL7 to enhance the activity of EGFL7 for the treatment of tumours (U.S. Pat. No. 7,947,278).
There is still a need for alternative imaging approaches that can aid in estimating vessel shape and size and to identify different approaches for targeting EGFL7.